Regulation of fundamental stem cell behavior using two-dimensional synthetic templates in vitro is of immense importance in regenerative medicine. In particular, human mesenchymal stem cells (hMSCs) are of great interest due to their ability to undergo multilineage differentiation, and derivation from adult tissues. Control over cell behaviors such as adhesion, proliferation and differentiation is likely to facilitate increased therapeutic applications of stem cells. However, the inherent complexity of the native extracellular microenvironment makes decoupling the cause and effect of particular signaling cues (e.g. proteins, soluble factors, cell-cell interactions) difficult. For a true understanding of the identity and concentration of extracellular matrix fragments (peptides) necessary for even simple stem cell adhesion, the microenvironment needs to be simplified. Although growing cells on a chemically defined surface, where cell-surface interactions are known and quantifiable, is desired, it is rarely achieved. Cells are traditionally grown on tissue culture polystyrene (TCPS), which, like most other materials, undergoes rapid adsorption of proteins in biological fluid, creating a poorly defined interface for cell studies, where identity, density and orientation of the biomolecules is unknown. Hence, a large amount of research has focused on creating synthetic two-dimensional templates for chemically defined cell culture and expansion including self-assembled monolayers (SAMs), hydrogels, polymer brushes, thin films, and layer by layer films. To better regulate cell-template interactions common synthetic templates employ poly(ethylene glycol) (PEG) to provide a “blank slate” background to cells. PEG, when used in combination with specific peptides on synthetic templates, can provide a powerful platform for regulating stem cell behavior.
Polymer coatings are one of the few templates that are compatible with a wide range of substrates and have good physical stability. However, the polymer coating must remain insoluble and not delaminate from the underlying substrate for the duration of the cell culture. This limits the composition of the polymers that can be used.